Pharmaceutical Composition and Galenic Form Corresponding to Rapid Oral Disintegration and Method for Production of Said Composition

Abstract

The invention is based on a known method for the cold rolling of metallic rolled stock ( 4 ), which for plastic deformation enters a roll gap ( 3 ) formed between oppositely rotating rolls ( 1, 2 ) on a run-in side and leaves the roll gap on a run-out side, deformation heat that is produced being removed by supplying an industrial gas which is at a lower temperature than the rolled stock. In order on this basis to provide a cold rolling method with which, on the one hand, corrosion of the surfaces of the rolled stock and the surfaces of the rolls in the region of the roll .gap is effectively prevented and with which, on the other hand, condensation of moisture on the rolls and a reduction of the oxygen content of the ambient air of relevance to health as a result of the supply of large amounts of inert gas are avoided, it is proposed according to the invention that a measured value for the surface temperature of at least one of the rolls is determined, and that the supply of industrial gas is set on the basis of the measured value.

1 . A pulverulent pharmaceutical composition which can be used for constituting, after compression, a galenic form giving rapid oral disintegration, said composition comprising solid particles based on a mixture of excipients which comprises at least one diluent, said particles being coated with a film based on an aqueous colloidal solution which is provided for prehydrating said composition, such that said particles thus coated are free from one another in said composition, characterized in that said colloidal solution comprises a self-emulsifying system comprising, in combination: 
 at least one hydrophilic film-forming compound,    at least one lubricating amphiphilic compound, and    at least one humectant amphiphilic compound.    
     
     
         2 . The pharmaceutical composition as claimed in  claim 1 , characterized in that the mass fraction of said colloidal solution in the dry state in said composition falls within a range of from 0.01% to 10%.  
     
     
         3 . The pharmaceutical composition as claimed in  claim 2 , characterized in that the mass fraction of said colloidal solution in the dry state in said composition falls within a range of from 0.1% to 5%.  
     
     
         4 . The pharmaceutical composition as claimed in  claim 3 , characterized in that the mass fraction of said colloidal solution in the dry state in said composition falls within a range of from 0.5% to 3%.  
     
     
         5 . The pharmaceutical composition as claimed  claim 1 , characterized in that said hydrophilic film-forming compound is a solid which is pulverulent at a temperature of 25° C., which is chosen from the group consisting of carbohydrates, polyethylene glycols, polysaccharides, gum derivatives, polyglyceride derivatives, and mixtures of several of these compounds.  
     
     
         6 . The pharmaceutical composition as claimed in  claim 5 , characterized in that said hydrophilic film-forming compound is a carbohydrate chosen from the group consisting of maltodextrins, dextrins, sorbitol, mannitol and xylitol.  
     
     
         7 . The pharmaceutical composition as claimed in  claim 5 , characterized in that said hydrophilic film-forming compound is a polyethylene glycol of weight-average molecular mass Mw ranging from 1000 g/mol to 6000 g/mol.  
     
     
         8 . The pharmaceutical composition as claimed in  claim 5 , characterized in that said hydrophilic film-forming compound is a polyglyceride derivative chosen from the group consisting of lauroyl macrogolglycerides or stearoyl macrogolglycerides.  
     
     
         9 . The pharmaceutical composition as claimed in  claim 1 , characterized in that said lubricating amphiphilic compound is chosen from the group consisting of sodium docusate, sodium lauryl ether sulfate, sodium lauryl sulfate, glycerol derivatives, polyethylene glycols, leucine, stearic acid, magnesium stearate, sodium stearyl fumarate and sodium benzoate.  
     
     
         10 . The pharmaceutical composition as claimed in  claim 1 , characterized in that said humectant amphiphilic compound is chosen from the group consisting of lipoamino acids, sorbitans and their ethoxylated derivatives, lecithin derivatives, polyethylene glycol derivatives, polyglyceride derivatives, poloxamers, sugars and sugar derivatives.  
     
     
         11 . The pharmaceutical composition as claimed in  claim 10 , characterized in that said humectant amphiphilic compound is a poloxamer.  
     
     
         12 . The pharmaceutical composition as claimed in  claim 10 , characterized in that said humectant amphiphilic compound is a polyethylene glycol derivative chosen from the group consisting of cetomacrogols 1000 and macrogol-25 cetostearyl ethers.  
     
     
         13 . The pharmaceutical composition as claimed in  claim 10 , characterized in that said humectant amphiphilic compound is a polyglyceride derivative of lauroyl macrogolglyceride or stearoyl macrogolglyceride type.  
     
     
         14 . The pharmaceutical composition as claimed in  claim 1 , characterized in that said or each diluent is soluble in an aqueous medium of water or saliva type or is capable of swelling in said aqueous medium, said diluent(s) being present in said composition according to a total mass fraction ranging from 30% to 90%.  
     
     
         15 . The pharmaceutical composition as claimed in  claim 14 , characterized in that said or at least one of said diluent(s) is a water-soluble diluent which is chosen from the group consisting of sugar derivatives, dextrins and maltodextrins.  
     
     
         16 . The pharmaceutical composition as claimed in  claim 15 , characterized in that said or at least one of said diluent(s) comprises a sugar derivative chosen from the group consisting of lactose, sucrose, trehalose, mannitol, sorbitol, erythritol, maltitol, lactitol and fructose.  
     
     
         17 . The pharmaceutical composition as claimed in  claim 14 , characterized in that said or at least one of said diluent(s) is a diluent capable of swelling in an aqueous medium, which is chosen from the group consisting of starch derivatives, pregelatinized starches, modified starches, gum derivatives, derivatives of microcrystalline cellulose, and silica derivatives.  
     
     
         18 . The pharmaceutical composition as claimed in  claim 1 , characterized in that said mixture of excipients also comprises at least one cohesion agent, such as microcrystalline cellulose or one of its derivatives, a dextrin, a lactose, a calcium phosphate derivative or a starch derivative, said cohesion agent(s) being present in said composition according to a mass fraction ranging from 0.1% to 40%.  
     
     
         19 . The pharmaceutical composition as claimed in  claim 1 , characterized in that it has, before compression, an apparent density, measured according to the European Pharmacopoeia, which falls within a range of from 0.4 to 0.9 g/ml.  
     
     
         20 . The pharmaceutical composition as claimed in  claim 1 , characterized in that it comprises at least one active ingredient in the dispersed state in said mixture of excipients.  
     
     
         21 . A galenic form giving rapid oral disintegration and comprising an uncoated tablet, characterized in that said tablet consists of a pharmaceutical composition as claimed in  claim 1 .  
     
     
         22 . The galenic form as claimed in  claim 21 , characterized in that said tablet has a friability, measured in accordance with the European Pharmacopoeia, which is less than 1%.  
     
     
         23 . The galenic form as claimed in  claim 21 , characterized in that said tablet has a breaking strength, measured in accordance with the European Pharmacopoeia, which is greater than 15 Newtons.  
     
     
         24 . A method for producing a pharmaceutical composition comprising the following steps: 
 a) an aqueous colloidal solution of oil-in-water or water-in-oil type comprising, firstly, an aqueous phase and, secondly, a self-emulsifying system is prepared;    b) the colloidal solution obtained in a) is sprayed:    (i) onto solid particles consisting of an active ingredient dispersed in a mixture of excipients comprising at least one diluent, or    (ii) onto solid particles consisting only of said mixture of excipients, 
 in such a way that the (sprayable colloidal solution/particles intended to receive said colloidal solution) mass ratio is less than or equal to 10%;  
   c) the colloidal solution sprayed in b) is dried so as to obtain: 
 in case (i), said pharmaceutical composition consisting of said solid particles comprising said active ingredient, which are coated with a film; or  
 in case (ii), an intermediate composition consisting of said solid particles of excipients, which are coated with said film, and then  
   d) optionally, in this case (ii), said active ingredient is dispersed in said intermediate composition obtained in c), so as to obtain said pharmaceutical composition.    
     
     
         25 . The method as claimed in  claim 24 , characterized in that said self-emulsifying system comprises, in combination: 
 at least one hydrophilic film-forming compound, such as a solid which is pulverulent at a temperature of 25° C., which is chosen from the group consisting of carbohydrates, polyethylene glycols, polyglyceride derivatives, and mixtures of several of these compounds,    at least one lubricating amphiphilic compound, such as a compound chosen from the group consisting of sodium docusate, sodium lauryl ether sulfate, sodium lauryl sulfate, glycerol derivatives, polyethylene glycols, leucine, stearic acid, magnesium stearate, sodium stearyl fumarate and sodium benzoate, and    at least one humectant amphiphilic compound, such as a compound chosen from the group consisting of lipoamino acids, sorbitans and their ethoxylated derivatives, lecithin derivatives, polyethylene glycol derivatives, polyglyceride derivatives, poloxamers, sugars and sugar derivatives.    
     
     
         26 . The method as claimed in  claim 24 , characterized in that said colloidal solution prepared in step a) comprises: 
 a mass fraction of said self-emulsifying system of less than or equal to 10%, and    a mass fraction of water greater than or equal to 90%.    
     
     
         27 . The method as claimed in  claim 24 , characterized in that step b) is carried out at a temperature ranging from 40° C. to 70° C.  
     
     
         28 . The method as claimed in  claim 24 , characterized in that the viscosity at 50° C. of said colloidal solution to be sprayed in step b) falls within a range of from 2 mPa·s to 40 mPa·s.  
     
     
         29 . The method as claimed in  claim 24 , characterized in that the ratio of the apparent density of the composition obtained in step c) or d) to the apparent density of the solid particles before spraying is between 1 and 1.2.